The goal of this project is to study the host response to onchocercal infection in order to understand the pathogenesis of clinical disease, the immune mechanisms important in the persistence of the parasite within the host and in protective immunity, and to develop improved immunodiagnostic techniques. The initial phase has involved detailed clinical and laboratory assessment of the severe side effects (Mazzotti reaction) that accompany treatment of the infection and limit the potential of mass chemotherapy for onchocerciasis. Twenty-five patients were treated at a research center in Ghana and subjected to intensive immunologic and clinical evaluation during their Mazzotti reactions. Most prominent of the immunological changes was a dramatic fall of serum complement levels within 2 hours of initiating treatment and evidence for activation of immediate hypersensitivity immune mechanisms including evidence of eosinophil and most cell degranulation both morphologic around microfilariae being killed in the skin as well as biochemically with rises in serum eosinophil granule protein concentrations and urinary histamine output. Correlation between individual clinical responses with these and other immunologic changes is currently underway. Also in progress is a study of the immunopathology of onchocercal eye lesions using ocular tissue and fluids removed from patients at the time of cataract surgery.